VEGF is known as vascular permeability factor but recent studies report that VEGF is major angiogenesis factor in human skin. Therefore, VEGF is a molecule which attracts attention in fields of studies on healing of wound, improvement of skin color, hair growing/hair restoration, and the like.
In normal skin, VEGF is secreted from epidermal keratinocytes in a small amount and is bound to a specific receptor which is present on dermal microvascular endothelial cells. As a result, viability of the endothelial cells is kept to maintain upper blood vessels having reticular structures.
It has been reported that VEGF in the epidermis thickened during inflammation or healing of wound is very highly expressed, which leads to an increase in blood vessels and supply of nutrients (Non Patent Document 1). Further, it has been reported that, in the hair anagen phase, blood vessels around the hair follicle are drastically dilated and VEGF is expressed in cells of the hair follicle, while in the hair catagen and telogen phases, expression of VEGF is suppressed by regression of the blood vessels (Non Patent Document 2).
It has further been reported that VEGF promotes vascular formation, and hence promotes blood circulation to supply large amounts of nutrients to hair roots and is related to adhesion between hair cortex cells.
In particular, a recent study reports that a decrease in VEGF expression level is correlated with a decrease in hair firmness and elasticity, and application of a VEGF production promoter to a hair cosmetic has been a focus of attention (Non Patent Document 5).
Therefore, promotion of production of VEGF, which is involved in the increase in blood vessels and supply of nutrients in the dermis is very effective not only for recovery/healing of wound but also for improvement of skin color such as dullness or decreased transparency of skin caused by lowered skin metabolism or the like. In addition, promotion of production of VEGF, which is also involved in growth of hair/hair follicle is effective for prevention and improvement of symptoms such as hair loss/thin hair and decreased hair firmness and elasticity.
In view of the foregoing, various VEGF production promoters have been developed so far. For example, the following preparation and extracts have been reported to have VEGF production promoting activities: a preparation derived from soybean (Patent Document 1); an extract of each of Boletinus cavipes, Suillus laricinus, Suillus grevillei, Boletinus asiaticus, Suillus bovinus, Suillus spectabilis, Acanthopanax senticosus Harms, polygonatum rhizome, Gentiana lutea, Alexandrian Senna, Eucommia ulmoides, rhubarb, melilot, coix seed, Chinese wolfberry fruit, Japanese Angelica Root, rehmannia root, gardenia fruit, Glycyrrhiza, carrot, red ginseng, lithospermum root, and cymbidium (Patent Document 2); an extract of a plant belonging to the genus Pandanus (Pandanus L.f.) (Patent Document 3); and an extract of each of shiitake mushroom, Echinacea purpurea, prune, bean sprouts, and jiaogulan (Patent Document 4). However, blending of each of the VEGF production promoters may be limited from the viewpoint of a side effect, and blending of each of the promoters in an effective amount may cause a problem such as coloring or unpleasant odor.
On the other hand, it has been reported that the cycloartane-type glycoside is isolated from a plant belonging to the genus Cimicifuga of the family Ranunculaceae such as Cimicifuga simplex and has pharmacological activities such as an thymidine intake inhibitory activity (Non Patent Document 3) and an antimalarial activity (Non Patent Document 4).
However, it was not known that the cycloartane-type glycoside has any VEGF production promoting activity.